Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis
Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis
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DOI：
10.1016/j.bbadva.2023.100078
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发表时间：
2023-01-01
期刊：
影响因子：
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通讯作者：
Shimano，Hitoshi
中科院分区：
文献类型：
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作者：
Istiqamah，Nurani;Matsuzaka，Takashi;Shimano，Hitoshi
脂肪酸延长酶6（C16：0）通过催化棕榈酸酯（C16：0）延长为硬脂酸酯（C18：0）和棕榈油酸酯（C16：1 n-7）延长为疫苗（C18：1 n-7）来控制细胞脂肪酸（FA）组成。尽管对p53 VL 6的转录调控已经有了很好的研究，但p53 VL 6的转录后调控还不完全清楚。因此，本研究旨在评估microRNAs（miRNAs）在调节人类VL 6中的作用。生物信息学分析鉴定了5种可能与VL 63 ′-非翻译区（UTR）结合的miRNAs：miR-135 b-5 p、miR-135 a-5 p、miR-125 a-5 p、miR-125 b-5 p和miR-22- 3 p。双荧光素酶检测结果显示，这些miRNAs通过直接作用于p53 VL 6 mRNA的3′-UTR而下调p53 VL 6。此外，miR-135 b-5 p和miR-135 a-5 p通过在mRNA和蛋白水平上抑制VL 6而抑制多形性胶质母细胞瘤细胞的细胞增殖和迁移。综上所述，我们的研究结果提供了新的调节机制，为novel VL 6在转录后水平，并确定潜在的候选人与多形性胶质母细胞瘤患者的治疗。
ELOVL fatty acid elongase 6 (ELOVL6) controls cellular fatty acid (FA) composition by catalyzing the elongation of palmitate (C16:0) to stearate (C18:0) and palmitoleate (C16:1n-7) to vaccinate (C18:1n-7). Although the transcriptional regulation ofELOVL6has been well studied, the post-transcriptional regulation ofELOVL6is not fully understood. Therefore, this study aims to evaluate the role of microRNAs (miRNAs) in regulating humanELOVL6. Bioinformatic analysis identified five putative miRNAs: miR-135b-5p, miR-135a-5p, miR-125a-5p, miR-125b-5p, and miR-22–3p, which potentially bindELOVL63′-untranslated region (UTR). Results from dual-luciferase assays revealed that these miRNAs downregulateELOVL6by directly interacting with the 3′-UTR ofELOVL6mRNA. Moreover, miR-135b-5p and miR-135a-5p suppress cell proliferation and migration in glioblastoma multiforme cells by inhibitingELOVL6at the mRNA and protein levels. Taken together, our results provide novel regulatory mechanisms forELOVL6at the post-transcriptional level and identify potential candidates for the treatment of patients with glioblastoma multiforme.